Plasma amyloid assay as a pre-screening tool for amyloid positron emission tomography imaging in early stage Alzheimer's disease

Abstract

Introduction: Due to the high cost and high failure rate of ascertaining amyloid positron emission tomography positivity (PET+) in patients with earlier stage Alzheimer's disease (AD), an effective pre-screening tool for amyloid PET scans is needed. Methods: Patients with mild cognitive impairment (n = 33, 24.2% PET+, 42% females, age 74.4 ± 7.5, MMSE 26.8 ± 1.9) and mild dementia (n = 19, 63.6% PET+, 36.3% females, age 73.0 ± 9.3, MMSE 22.6 ± 2.0) were recruited. Amyloid PET imaging, Apolipoprotein E (APOE) genotyping, and plasma amyloid β (Aβ)1-40, Aβ1-42, and total tau protein quantification by immunomagnetic reduction (IMR) method were performed. Receiver operating characteristics (ROC) analysis and Youden's index were performed to identify possible cut-off points, clinical sensitivities/specificities, and areas under the curve (AUCs). Results: Amyloid PET+ participants had lower plasma Aβ1-42 levels than amyloid PET-negative (PET-) subjects. APOE ϵ4 carriers had higher plasma Aβ1-42 than non-carriers. We developed an algorithm involving the combination of plasma Aβ1-42 and APOE genotyping. The success rate for detecting amyloid PET+ patients effectively increased from 42.3 to 70.4% among clinically suspected MCI and mild dementia patients. Conclusions: Our results demonstrate the possibility of utilizing APOE genotypes in combination with plasma Aβ1-42 levels as a pre-screening tool for predicting the positivity of amyloid PET findings in early stage dementia patients.